Understanding the cellular and molecular mechanisms of hazardous chemicals in our environment is a critical national objective. CERCLA was established to gain knowledge on the public health risks associated with exposure to Superfund site hazardous waste. Thus, a greater understanding of the exposure pathway and the health consequences resulting from human exposure to uncontrolled hazardous waste from Superfund sites are high priorities. The goals of the UC San Diego Superfund Basic Research Program are to implement modern scientific approaches to identify and characterize genomic stress responses elicited by water borne pollutants found at Superfund sites. Because such chemical exposure leads to alterations in patterns of gene expression, defining the underlying signal transduction pathways, characterization of the targeted genetic elements and established of the functional significance of these genetic changes are essential for understanding the impact of exposure to Superfund site chemicals on human health. Our experimental strategies, which are heavily upon recombinant DNA techniques and the development of new technologies, will yield new perspectives on monitoring, remediation and mechanisms of toxicity mediated through altered gene expression and aberrant cellular signaling. To meet these goals, the UC San Diego Superfund Basic Research Program will develop a multi-disciplinary effort consisting of 7 biomedical research projects and 3 research support cores. The research will be supported in part by a Ph.D. training program. The environmental problems resulting from our location in a coastal environment and our proximity to a populated border creates unique environmental US/Mexico border issues that are of special relevance to water born pollutants. These issues will be addressed through education in the community, in the industrial sector and the EPA Region 9 level by our Outreach Program and Government liaison efforts. Investigators with complementary expertise from 10 UCSD Departments, Organized Research Units and Centers are participating in this project. Our combined efforts are anticipated to provide new insights into the molecular mechanisms that lead to illnesses arising from environmental sources and to improve our understanding of the consequences of exposure to Superfund site contaminants.